This application proposes to investigate the mediating role of endocrine consequences on the occurrence of mental health outcomes that take place among HIV-1+ IDUs. Injecting drug use (IDU) is one of the major risk factors for contracting human-immunodeficiency virus, type-i, (HIV-1) infection. abnormalities in various endocrine systems develop in IDUs and HIV-1+IDUs and may be associated with number of mental health outcomes. Our earlier reports show that the ACTH and cortisol responses to a cold pressor challenge are attenuated in HIV-1 + individuals and, thus, support the proposed hypothesis. An array of outcomes including, anxiety, depression, and perceived psychological distress and difficulty adapting to stressors occurs in HIV-1 + IDUs. Since HIV is present in the brain soon after infection and esides in very high concentrations in the hippocampus, it is proposed that different endocrine systems are likely to be adversely impacted centrally in HIV-1 infection. It is important to understand the mechanisms involved in the development of neuroendocrine abnormalities - central or peripheral - in order to intervene n mental health-related problems. This five-year proposal investigates the responses of the thyroid and gonads to trophic hormones, hyroid releasing hormone (TRH), and luteinizing hormone-releasing hormone (LHRH), as well as adrenal Aictivity in response to a low-dose ACTH challenge. This investigation will be carried out using a crossectional three-group design (HIV-i+ lDUs, N+1OO, HIV-1- IDUs, N=100, and HIV-1- non-IDUs, N=100) with the total N = 300, X 3 ethnicitlies (African-Americans, Hispanics, Caucasians) X 2 genders (Women and Men). Only those HIV seropostiive subjects who do not have AIDS-defining symptoms and are not being treated with triple-drug therapy will be enrolled since the effect of triple-drug therapy on the endocrine system is unknown at this time. It is proposed to investigate whether the endocrine responses nediate mental health outcomes (i.e., depression, anxiety, and perceived psychological distress). These data will be useful in designing suitable interventions.